The proposed research program is an investigation of the relationship between form and function in macromolecular assemblies. Using the combined techniques of electron microscopy and X-ray diffraction, we propose to produce images showing the arrangement of the component subunits. We are studying two important kinds of subcellular structures: the multienzyme complex and actin. The alpha-ketoacid dehydrogenases are complexes of three component enzymes. Their size makes it possible to attack their structure with electron microscopy and solution X-ray scattering. The aim of our work is to determine the structure and thereby understand the organization. The second system we are studying is actin, a protein important in cellular motility. We are carrying out structural studies on bundle of actin, a common form of actin in nonmuscle cells. We propose to study the structural organization and attempt to understand the dynamic properties of these bundles. Both these structures have an unusual feature. They correspond to structures in which the components have higher symmetry than the final structure. The symmetry of the components is generated by the specific interaction of their identical protein subunits. When these component subassemblies interact the overall symmetry is reduced. The significance and occurrence of this phenomenon is only beginning to be appreciated.